… or Why I Became a Clinical Research Professional.

It all started because of a commitment I made when I was too young to understand into what I was getting myself. My mother had headaches, you see. Not the usual “throbbing-in-the-temples” kind of headaches, but the “gut-wrenching, totally incapacitating, rip-the-carpet-out-with-your-bare-hands” kind of headaches. Migraine, cluster headache, trigeminal neuralgia—whatever the flavor, they were bad. Really bad.

She saw practically every headache specialist in the country. They gave her ergotamine injections until her fingers turned blue, narcotics powerful enough to stop a charging elephant, and dozens of other medications, many of which were experimental at the time. Nothing worked.

So, I made a commitment to help find an answer. It was a promise I made to myself—an altruistic, if somewhat self-serving, pledge. I didn’t just want to help my mother. I wanted to ensure that no one, including frightened young children like myself, would ever again have to endure, or witness, such agony. Medical school was out of the question. I was still a kid, and the thought of staying in school until I was 30 was more than I could bear. It didn’t help that I was squeamish and often came down with an exotic disease on any day my class was scheduled to dissect a frog in biology class.

I went to pharmacy school instead. After graduating, I went to work for a pharmaceutical company working in the field of analgesics. My first assignment was developing “Harter Tables” — affectionately named for the FDA reviewer who so politely requested that we compile them — comparing pre- and posttreatment changes in laboratory values for a pediatric product’s new drug application. It was shortly after this tedious effort that I learned the first of several important lessons about pharmaceutical research and development: It’s a competitive business.

My company’s baby, the product of adoring labor and nurturing love, reached the market. But we never got the chance to sell it under our label. Lacking a large sales force, our company signed a co-branding agreement with a much larger pharmaceutical giant. The original deal was that we would have exclusivity for the prescription market; they would have the over-the-counter market once the product went off-patent. Unfortunately, they had better lawyers.

So we embarked on an even nobler quest. Our company’s crack team of chemists found that dogs, when given an experimental antimalarial, had an unexpected reaction: their blood pressure dropped. Eureka! A new treatment for hypertension! And don't worry, the dogs are fine.

Unfortunately, after a year or two of intensive testing—this time on human volunteers—and after investing a measly $100 million or so, we discovered that it also increased heart rate. The increase was so slight it took dozens of patients across several trials to demonstrate it statistically. That outcome meant sudden death to the idea of marketing the drug as an antihypertensive agent. Lesson #2: pharmaceutical research is difficult, expensive, time consuming, and RISKY!

Ok, so our fledgling new drug didn’t cure malaria and it made a lousy antihypertensive, but it still was a novel chemical entity yielding extensive improvement in cardiac output. “We’ve got a fantastic new treatment for congestive heart failure here,” we said––or so we hoped.

This next time around, our company pursued a simultaneous worldwide regulatory submission that took seven years and half a billion dollars. The drug showed astonishing improvements in cardiac hemodynamic parameters and quality-of-life measures. Study coordinators were brandishing thank-you letters from patients attesting to a a return to productive lives. Before taking the drug, many of these patients had been basically bedridden, unable to walk even a few yards or to climb a single flight of stairs. It was the kind of result that makes the hair on the back of the neck of an idealistic young pharmacist tingle—a treatment that could potentially relieve the suffering of millions. Noble stuff.

At that time, it was one of the most intensively researched new CHF treatments ever to reach the marketplace. Although regulatory authorities didn’t require it then, we decided to add a multicountry, long-term, 4,000-patient survival trial to the dossier, mostly to jazz up our marketing punch. Unfortunately, we learned something that a lot of other pharmaceutical companies and their patients have learned in the years since: Sometimes, adverse events don’t manifest themselves until thousands of patients are exposed to a new drug. Then they miraculously appear on the front page of the newspaper and on the nightly news.

Even after studying new investigational medical products for years, if not decades, before they reach the market, there is still really no way to know until it’s too late what unfavorable reaction might rear its ugly head. Approval from FDA or other regulatory agencies does not guarantee that a new compound has no adverse effects or even that scientists know everything there is to know about it. It simply means that the drug has been adequately tested across a representative sample of the population, and the benefits offered by the product, according to the best economically feasible statistical sampling methods, outweigh the risks associated with its use.

Meanwhile, the consumer press bombards the public with horror stories of how an incompetent FDA was too quick to approve an obviously dangerous drug. And before a pharmaceutical company can even verify an early report of an unexpected adverse effect, the airwaves are filled with ads for lawyers who promise to stick it to that cold-hearted pharmaceutical giant that pushed through a toxic brew in a plot to boost corporate profits. And let’s not talk about that greedy pharmacist with a mere six years of education that charged an outrageous fee (a whole $2.50 above cost) just to count the pills and slap on a label. Give me a break.

The public wants the impossible. Patients want an endless parade of innovative and effective new medical products to be available immediately upon initial discovery, at virtually no cost, with an iron-clad guarantee of no side effects. It’s enough to make a former pharmacist leave his patients to fend for themselves.{quote_middle}

But, darn it, there is still that integrity thing. I made a commitment to myself, if not to all of mankind, to help develop cures—or at least safe and effective medical treatments—for all the diseases and discomforts in the world. So what if, in the naiveté of youth, I didn’t stop to examine whether my goal was a little too lofty or my scope too grandiose? It doesn’t matter that this is a competitive, difficult, and risky industry or that it is physically impossible to satisfy our customers’ unyielding desire for a miracle. A promise is a promise.

For Patients AND Profits

It’s difficult to just abandon a long career in this industry. Our tasks are Herculean, our journey treacherous, and our plunder sometimes dispiriting, but we can’t abandon our quest. Maybe not everyone can trace their reasons for joining the industry back to some childhood commitment, but many chose a career in medical product development because of the positive impact they could have on millions of people in dire need of help. In the day-to-day events of a complex modern existence, we may lose sight of that admirable, if not entirely altruistic, vision. Still, it remains, lurking in the depths like an anchor line, keeping us steadfastly moored in our important industry roles. We’ve still got to find that cure and get it to market for that poor woman with the bloody carpet burns on her fingers and the agonizing screams for relief from unbearable pain. A quest cannot be denied.

Of course, stockholders—the people that provide the enormous investments required to conduct medical research—expect to make a profit, and they fully deserve it. This is a risky business where fortunes can be lost in a single newscast, and those who invest in it are saints in my book, whether they purchase stock in a public company, invest time, energy, and maybe a little of their souls as pharmaceutical company employees, or put their life savings, and perhaps a little of their sanity, into building a contract research organization.

And with profit comes competition: Adam Smith’s so-called invisible hand that theoretically drives investment toward the areas where it will do the most good. Of course, that same hand can also slap you hard across the face, often when you don’t even deserve it. I won’t claim that it makes anyone stronger in the process. I’m idealistic, not stupid. But in the end, humanity is usually better off with competition than without it. How else would we ever be motivated to ever try developing medicines faster, cheaper, and with virtually no side effects?

During my career, our industry has made great strides in treating intractable headaches and a host of other serious or simply bothersome maladies. After the first few heart-wrenching failures, I eventually helped bring several wonderful products to market, including various therapies for migraine headache that finally offer my mother some relief. And I’ve come to recognize that it’s just as personally gratifying — although certainly not as financially rewarding — to be part of keeping less-than-perfect drugs off the market as it is to get the better ones there.

This article was originally published in the December 2001 issue of Pharmaceutical Executive.